PIPELINE

A BROAD PIPELINE OF T CELL THERAPIES FOR SOLID AND HEMATOLOGIC CANCERS

We have built a robust pipeline of TRuC-T cell product candidates for solid and hematologic cancers.

The versatility of our platform is highlighted by the multiple programs and multiple formats of the product candidates in our pipeline. In preclinical studies with TRuC-T cell product candidates, we have shown better anti-tumor activity, longer persistence, and lower cytokine release compared to CAR-T cells bearing the same tumor antigen binding domains. Our lead candidate, TC-210, is expected to enter the clinic in early 2019.

TC-210

Our most advanced TRuC-T cell product candidate is TC-210, which targets mesothelin-positive solid tumors. While its expression in normal tissues is low, mesothelin is highly expressed in many solid tumors. Mesothelin overexpression has also been correlated with poorer prognosis in certain cancer types and plays a role in tumorigenesis.

The cancer types that we intend to treat in our planned Phase 1/2 clinical trial include non-small cell lung cancer, ovarian cancer, malignant pleural mesothelioma and cholangiocarcinoma. These cancers represent a patient population of up to 81,000 in the United States alone.

In our preclinical studies we have demonstrated better anti-tumor activity and persistence of TRuC-T cells compared to CAR-T cells while also exhibiting lower levels of cytokine release. We conducted a pre-IND meeting with the FDA in February 2018 and expect to file an IND for TC-210 early in 2019.

TC-220

We are currently conducting IND-enabling studies for our mono TRuC-T cell product candidate, TC-220, targeting MUC16-positive solid tumors. While its expression in normal tissues is low, MUC16 is highly expressed in many solid tumors, including ovarian, pancreatic, gastric and colorectal cancers. We plan to develop TC-220 initially for the treatment of MUC16 overexpressing ovarian cancer, which represents a patient population of up to 17,000 in the United States alone.

TC-110

We are also developing a mono TRuC-T cell, TC-110, targeting CD19-positive B-cell hematological malignancies, to improve upon and address the unmet needs of current CD19-directed CAR T cell therapies. The clinical development plan for TC-110 will initially focus on three specific areas: adult acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). These are indications for which CAR-T cells have either been approved but have room for efficacy improvement (specifically, DLBCL), proven to be too toxic for use (specifically, adult ALL), or have not been approved at all (specifically, FL).

Our preclinical data indicate that TC-110 is superior to CD19-CAR-T cells (carrying either 4-1BB or CD28 co-stimulatory domains) both in anti-tumor activity as well as the level of cytokine release which may translate into lower rates of adverse events.

Dual TRuC Programs

We are developing dual TRuC-T cells, including the TC-310 and TC-410 programs, designed to reduce the potential for antigen escape in solid tumors or hematological malignancies by targeting more than one cancer antigen. These second generation TRuC-T cells are also able to integrate platform enhancements to counter the hostile tumor microenvironment.

Enhancements

We are focused on continued innovation to broaden our platform through internal research and collaboration with leading academic laboratories and industry partners in the field of T-cell immunology, cell therapy, gene editing, and process development. We are developing several enhancements to control on-target, off-tumor activity and counter the immunosuppressive microenvironment of solid tumors. These include mechanisms to block a key cancer defense known as the PD-1/PD-L1 pathway.